In 1992, it is estimated that more than 20,000 new cases of ovarian cancer will be diagnosed in the United States, and 12,000 women will die of this disease. These statistics place ovarian carcinoma as the most frequent cause of death due to gynecological malignancies, and fifth overall as a cause of death from cancer in women. Though the cure rate for ovarian cancer diagnosed at Stage I may approach 90%, the majority of cases present at an advanced stage due to a paucity of clinical symptoms. The prognosis is poor, with an overall five-year survival below 30%. Methods which provide early detection of ovarian cancer may profoundly effect the mortality of this disease. In order to directly investigate the molecular genetic aberrations leading to altered gene expression in ovarian neoplasia, a panel of cell lines derived from patients with ovarian adenocarcinoma has been studied. These cell lines demonstrate significant differences in the ability to form tumors in clonogenic cell assays and nude mouse assays. Directional cDNA libraries from non-tumorigenic and highly-tumorigenic cell lines were constructed. Subtractive hybridization is used to enrich the libraries for either tumor-specific or normal-specific cDNAs. These differentially- expressed genes are then evaluated utilizing matched patient normal and tumor tissue samples to confirm normal and tumor specificity with the aim of identifying genes critical in the process of carcinogenesis (tumor- promoter genes), or for maintaining the normal state (tumor-suppressor genes). In addition, genes which can serve as useful markers for early disease may be revealed.